The focus of Core 2 is on biodegradable and biocompatible matrices to be used as custom-designed scaffolds in tissue engineering. Scaffolds will be optimized via chemistry and processing to interact with mesenchymal progenitor cells (MPCs) and human embryonic stem cells (hESCs) (Core 1) within environments of bioreactors (Core 3). Our aim is to gain fundamental insight into the communication between matrices and stem cells as a route to improve scaffold design and function. Our hypothesis is that an improved match between scaffold design (chemistry, morphology and structure from the molecular to macro-scale perspective) and stem cells will lead to improved structure and function of engineered tissues. The extent to which this improved 'communication' controls cell responses and tissue outcomes is virtually an untapped area of scientific inquiry. Thus there is a great deal of insight to be gained and applied to critical questions in biology related to surface interactions with cells. The available evidence in the literature, and from our own preliminary studies, suggests that this is an important topic that requires detailed inquiry in order to improve specific tissue engineering strategies. Matrix-cell relationships can be in the form of the chemical and/or physical interactions with the adherent cells. A key aspect of this core is the design and characterization of tissue engineering scaffolds with desired ranges of surface chemistries, degradation rates, mechanical properties and morphologies. Generating suitable polymer scaffolds is a critical step in functional tissue engineering and the team at Tufts has extensive experience in this area. We plan to build on our strong base of biopolymer synthesis and processing and associated inquiry into cell responses as a basis for this core activity.